title: In vivo anticoagulant effect of ethyl pyruvate in endotoxemic rats.
abstract: BACKGROUND
  Disseminated intravascular coagulation (DIC), a disorder of the blood coagulation function, is a common complication of severe sepsis. Ethyl pyruvate (EP), a derivative of pyruvate, is known for its anti-inflammatory and antioxidant properties. Recently, EP showed anticoagulant effects in vitro. Therefore, the aim of study is to investigate the in vivo anticoagulant effect of EP on a severe DIC model induced by lipopolysaccharide (LPS) in anesthetized Wistar rats.
  
  
  METHODS
  The animals were intravenously infused with LPS (30 mg/kg) over a period of 4h. One hour after LPS initiation, rats were treated with EP in three dosages (20, 40 and 60 mg/kg/4h, i.v.).
  
  
  RESULTS
  The intermediate and high doses of EP (40 and 60 mg/kg) prevented circulatory failure, improved renal and hepatic function, and reduced the plasma levels of TNF-α and IL-6 after LPS administration. All used doses of EP significantly prevented prothrombin time prolongation, and reduced mRNA expression of tissue factor in lung tissue induced by LPS. The two higher doses of EP attenuated plasma concentrations of thrombin-antithrombin complex. The high dose of EP (60 mg/kg) significantly preserved platelet counts, and improved survival rate. However, EP did not reduce the elevation of plasma plasminogen activator inhibitor-1 during endotoxemia.
  
  
  CONCLUSIONS
  EP demonstrates the in vivo anticoagulant effect and improved organ functions in a severe DIC model in rats, which is likely associated with the inhibitory effect on tissue factor mRNA expression and cytokines release. Its effectiveness in preventing DIC is not mediated by increase in fibrinolysis.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Kung
authors.forename: Yen-Mei
authors.initials: YM
authors.lastname: Lee
authors.forename: Mao-Hsiung
authors.initials: MH
authors.lastname: Yen
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000097:blood*; D006801:Humans; D008297:Male; D011773:Pyruvates / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY
chemical_list: D000925:Anticoagulants; D011773:Pyruvates; C046522:ethyl pyruvate